1. Technical Field
This document relates to polypeptide inhibitors of Smad3 polypeptide activities. For example, this document provides methods and materials for using polypeptides (e.g., polypeptides designed to include both a cell penetrating amino acid sequence and an amino acid segment of a SH3 domain of a SNX9 polypeptide) to inhibit one or more Smad3 polypeptide activities. This document also relates to methods and materials for using RNA interference to treat a disease (e.g., a fibrotic disease) in a mammal (e.g., a human).
2. Background Information
Transforming growth factor beta (TGFβ) is a 25 kDa polypeptide that regulates a variety of cellular processes including matrix deposition, mitosis, development, differentiation, and apoptosis. The primary intracellular mediators of TGFβ action are the Smad proteins, although non-Smad pathways have been reported, often in a cell-type specific context. Three general categories of Smad proteins were identified: receptor-regulated Smads (R-Smads; Smads2 and 3 for TGFβ or Activin and Smads1, 5, and 8 for BMPs); common-mediator Smad (Co-Smad; Smad4); and inhibitory Smads (I-Smads; Smads6 and 7). The R- and Co-Smad proteins shuttle continuously between the nucleus and cytoplasm in unstimulated cells as well as in the presence of TGFβ.